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![]() Vol.2, No.3, 205-211 (2010) Natural Science http://dx.doi.org/10.4236/ns.2010.23032 Copyright © 2010 SciRes. OPEN ACCESS The nature of neuronal words and language Morris Henry Baslow Nathan S. Kline Institute for Psychiatric Research, Center for Neurochemistry, New York, USA; [email protected] Received 5 December 2009; revised 13 January 2010; accepted 30 January 2010. ABSTRACT Individual neurons in the brain possess natural language in the form of energy-dependent ac- tion potentials or spikes (S) operating on a mil- lisecond timescale that, along with pauses (P) between spikes, constitute a two letter (S, P) “alphabet” that is used to generate meaningful frequency-encoded neuronal “words”. These words are then used to transmit information to other neurons in the form of phrases consisting of two or more words that are contained within longer pause-delineated structured declarative sentences. In this article, the nature of neuronal words and language are described, and exam- ples provided that illustrate the way in which neuronal language is used by the brain to in- teract with and interpret both its internal and external environments. It is hoped that a fuller understanding of the language used by neurons to communicate may lead to development of novel treatments for a number of human neu- ropathies. Keywords: Biosemiotics; Brain; Cognition; Language; Learning; Memory; Neurons 1. INTRODUCTION Semiotics is broadly defined as a study of signs, mean- ings and their significance in communication, and bio- semiotics as a study that is based on the general assertion that all living organisms including cells are semiotic systems. While information processing in the brain is highly complex, each neuron uses a simple code mecha- nism for transmitting information. This is in the form of electrophysiological action potentials or spikes (S) of about a 1 millisecond (ms) duration that, along with pauses (P) between spikes constitute a two letter “al- phabet” that generates meaningful frequency-encoded signals or neuronal S/P “words” [1]. The term “word” for neuronal activity in spikes/s has previously been used to describe the electrophysiological activity of the visual interneuron of the blowfly where each action potential (AP) was considered a “short” word and trains of AP’s considered “longer” words [2]. In this article a neuronal word is defined as a single AP together with the total pause before the next AP; a phrase is defined as a group of two or more words, and a sentence as a temporal grouping of such words containing a subject, and a predicate that expresses what is stated about the subject [1]. All neuron codes, whether continuous trains of spikes that are characteristic of information transmitted at low frequencies, or bursts of spikes that are character- istic of information transmitted at high frequencies, are made up of interactions between spikes and pauses. There are two theories regarding how these spikes carry encoded information [3]. One is the “spike rate code” which suggests that information is carried in the average rate at which the neuron fires, and that the timing of each spike is random. The other is the “spike timing code” that suggests that specific information is carried not only in the average spike rate at which a neuron fires, but also in the precise timings between each spike. In this article, it is proposed that neurons transmit meaningful informa- tion not only in their spike rate and spike pause timing, but also in the spike duration or length (SL) and its rela- tionship to the pause length (PL) between spikes. It is this relationship that constitutes a neuronal “S/P word”, and adds an additional dimension to the potential rich- ness of communication between neurons. 2. DISCUSSIONS 2.1 Anatomy of a Neuronal Word The communication method used by the brain is gener- ated at the cellular level where individual neurons trans- mit information to one another by generation a series of wave-like depolarizations. This depolarization’s start at the plasma membrane of their cell bodies (soma) and pass along the plasma membranes of axon hillocks, ax- ons and pre-synaptic dendrites. Each wave-like spike consists of two components, first, a rapid depolarization, involving the efflux of K+ and influx of Na+ at the plasma membrane down their respective intracellular/ extra cellular gradients, a process that requires little or ![]() M. H. Baslow / Natural Science 2 (2010) 205-211 Copyright © 2010 SciRes. OPEN ACCESS 206 no additional energy. This is followed by a re-polariza- tion process that occurs within an absolute refractory period during which time the intracellular negative membrane K+/Na+ potential is restored using energy derived from intracellular stores of adenosine triphos- phate (ATP) via a plasma membrane surface enzyme, Na+/K+ ATPase, in order to transport these ions against their respective gradients [4]. In single afferents of hu- man mechanoreceptive sensory nerve fibers of the skin of the hand, spike times-to-peak were 0.12-0.45 ms with a mean of 0.21 ms [5]. While the depolarization process is pre-energized and trigger-ready, re-polarization is a slower enzyme-dependent process that is subject to rate regulation by all factors that can affect enzyme activity. These include enzyme, substrate, and end-product con- centrations, focal ionic makeup, pH, temperature as well as the presence of competitive and non-competitive in- hibitors. All of these factors can affect the rate of re-polarization and the length of the absolute refractory period which in this study varied from 0.31-0.75 ms with a mean of 0.50 ms indicating that the energy consuming re-polarization period was 2.38 times longer than the depolarization period such that the length of the re-polarization period dominated the total spike period. In this study, the average length of a spike including the depolarization and longer re-polarization periods in the sensory nerve fibers was 0.71 ms with a range from 0.43-1.20 ms. The relationship between the depolariza- tion and re-polarization periods of a single spike is illus- trated in Figure 1. Since the depolarization is pre-primed and trigger ready, and the re-polarization period requires energy to reestablish ionic gradients, re-polarization is therefore subject to cellular control. Thus, the SL can be varied to incorporate information that is transmitted in the form of a SL/PL ratio over and above information that transmitted by Hz and/or specific peak-to-peak in- ter-spike intervals. Data from [5]. During the spiking process which includes the absolute refractory period, and until the ionic gradients are rees- tablished, a second spike cannot be generated. In addition, following the absolute refractory period there is a relative refractory period where only a strong stimulus can gener- ate a second AP, and following this period there is a pe- riod of longer pause with no electrophysiological activity. A spike including its absolute refractory period may vary, but an average spike-absolute refractive period length is about 1 ms, and is followed by a relative refractory pe- riod of about 2 ms in duration [6]. This in turn is fol- lowed by a pause of varying lengths before the next spike is generated. Thus, there are two phases of signal genera- tion, each consisting of two subcomponents. The total spike length (SL) is made up of the sum of the depolariza- tion and absolute refractory (re-polarization) periods, and the total pause length (PL) is made up of the relative re- fractory period and the pause until the next spike is initi- ated. The total pause length can vary from 0 to approxi- mately 10,000 ms under normal physiological conditions. Based on these neuronal spike and pause components, a single neuronal S/P word has been defined as the sum of its total spike length and its total pause length in ms, and different words are characterized by differences in the ratio of its SL to its PL [1]. The spike-generation process that results in S/P words is also is metabolically costly, calculated at 2.2 × 109 ATP molecules per spike [7], which requires that ATP supplies be constantly replenished or the timing of the spike-refractory periods will be altered, and meaningful frequency-encoded information lost [1]. An illustration of the components of a neuronal word as described is graphically presented in Figure 2. Figure 1. Cartoon showing the relative depolarization and repolarization times of a neuronal spike. ![]() M. H. Baslow / Natural Science 2 (2010) 205-211 Copyright © 2010 SciRes. OPEN ACCESS 207 Figure 2. Cartoon showing the components of the neuronal word, S1P7。 In this illustration, each neuronal word (S1P7 ) consists of a depolarizing spike (0.5 ms), an absolute refractory period when the plasma membrane is being re-polarized using ATP (0.5 ms) for a total spike length (SL) of 1.0 ms; a relative refractory period where the neuron can be ac- tivated but only by a strong stimulus (2.0 ms); and a period of inactivity (5.0 ms). The spike frequency is (1000 ms/8 ms) or 125 Hertz (Hz). Unless the pause is terminated by a second spike within a physiologically relevant period, the word is incomplete and without any quantitative meaning. Thus, a meaningful phrase must consist of at least two words, and a sentence of at least one phrase. The word S1P7 presented in this cartoon reflects the S/P message generated upon exposure of the isolated salt receptor of the blowfly to a 3 molar NaCl solution [8]. 2.2. Conversion of Frequency in Hz to S/P Words As shown in Figure 2, information contained in Hz for- mat differs from that in S/P word format in that in Hz, the signal is a measure of the time between two spikes that is initiated at the peak of the first spike and is con- stituted by the re-polarization period of that spike, its relative refractory period, the pause until initiation of a second spike and the depolarization period of a second spike. In essence, the signal recorded in Hz splits a spike into its two components such that a spike in Hz is a composite formed from elements of two AP’s. On the other hand, an S/P word as defined includes the depo- larization and re-polarization components of a single spike, along with the relative refractory period and the pause until the next spike is initiated. However, the two formats are clearly related, and while Hz is a commonly used method of recording and describing neuronal activ- ity, a reasonable estimation of the length of a neuronal word can also be derived from Hz. Thus, from Hz, the total time in ms of an average S+P word can be deter- mined: Total time per word: (SL + PL)ms = 1000/Hz. At a frequency of 100 Hz, the mean S+P word length would be 10 ms. However, the total value in ms for an S + P word does not provide sufficient information to con- struct a specific neuronal S/P word. For this, one re- quires in addition either the total spike length (SL) or total pause length (PL). Thus, for a SL of 0.5 at 100 Hz, the S/P word would be S0.5/P9.5, for an SL of 1.0, the S/P word would be S1.0/P9.0, and for a SL of 1.5, the S/P word would be S1.5/P8.5, representing three different S/P words out of a great number of possible S/P words that are dif- ferentiated by the relative lengths of their spikes and pauses. It is important to note that all of these S/P words are different and may transmit different meanings, but that all are being communicated at the same frequency of 100 Hz. Clearly, a measure of frequency alone for neuronal communications cannot be physiologically accurate. When afferent neuronal messages are con- verted from electrophysiological to chemical and back into electrophysiological messages at synaptic interfaces for transmission to efferent neurons, it is highly likely that differences in the SL/PL ratios are important ele- ments in modulation of the messages at these interfaces. Since much of the published neuronal response data is presented in the form of Hz, and while less accurate than actual S/P words, in the absence of a measured SL, and by using an average SL of 1.0, one can still derive useful information based on Hz about how neurons communi- cate with one another concerning the nature of their en- vironment. 2.3. Differences in Spike Rate, Spike Timing and Neuronal Word Codes in Information Transfer The spike rate code hypothesis proposes that information is processed in the form of the average time between ![]() M. H. Baslow / Natural Science 2 (2010) 205-211 Copyright © 2010 SciRes. OPEN ACCESS 208 spikes, and the spike timing code hypothesis proposes that information can also be contained in the differences in pauses between individual spikes, an analysis that can be used to identify harmonics and periodic oscillations in spike trains. Both of these hypotheses treat a spike as a point source and both are valid interpretations of re- corded data. However, these hypotheses are mirror im- ages of one another in that when viewed at the level of only two spikes, as presented in Figure 1, it is clear that the time between individual spikes treated as point sources, and the pause time between spikes will always be the same. On the other hand, the neuronal word code hypothesis as detailed above takes into consideration that individual spikes have a significant time dimension and shows that even at the level of only two spikes, there can be an enormous number of specific S/P words that can be generated and used to transmit different kinds of information. This is because each neuronal word is formed by individual components of the AP process as- sociated with spike generation, and differences in each component can alter the ratio between the total spike length and the total pause length. For the three examples provided above, S0.5/P 9.5, S1.0/P9.0 and S1.5/P8.5, their S/P ratios are 0.052, 0.111 and 0.176 respectively, and all are capable of being transmitted at the same frequency (Hz) where both the inter-spike time and pause time are the same. While all three hypotheses reflect frequency-based neuronal codes, the neuronal word code with its spike time dimension is the most physiologically realistic since it is the only one that identifies a mechanism whereby the AP can interact with the rate of depolariza- tion-induced release of neurotransmitters from pre- synaptic vesicles. Thus, only the neuronal word code appears to have the potential for an enhanced richness in information transfer, especially at the low frequencies and short periods dictated by ongoing bioenergetic and temporal physiological constraints. Moreover, measure- ment of the ratios that comprise S/P words may provide a new investigational tool, not available using the other “codes”, with which to assess differences in neuronal function between normal and pathological conditions. 2.4. Nature of Neuronal Language There are three components to neuronal language. First, neurons are “wired” in the sense that each neuron in the corpus occupies a specific place on a brain “map” of a given organism. Second, by virtue of its phenotype, each neuron sends specific kinds of messages for interpreta- tion within the CNS network. For environmental sensing neurons, these may identify the qualitative nature of the messages being communicated such as where in the brain or corpus it originates, and whether the message is a general call for stored information, or whether it is from a specific region associated with some specific factor such as sound, light or availability of “glucose” (Glc). Lastly, the messages sent by neurons must also concern the quantitative nature of sensed information such as the importance of message itself, or the specific levels of light, sound, pain, pressure, stretch, or sub- stance concentrations sensed. It is this last component, the quantitative nature of information within the brain, where specific frequency-encoded neuronal words ap- pear to play an important role. As an example, based on a recorded neuronal fre- quency of 100 Hz, a neuronal spike with a total spike length of 1 ms and a total pause length of 9 ms would constitute the neuronal S/P word ( S1P9) of 10 ms dura- tion. When this word is repeated, it becomes a phrase. In the blowfly, this phrase corresponds to immersion of its isolated salt receptor in 2.0 M NaCl [8]. Based on using a value for total SL of 1 ms, the specific words in “fly- speak” for immersion in additional NaCl concentrations of 0.5 and 1.0 M are S1P18 (52 Hz) and S1P12 (80 Hz) respectively. In addition, if the SL is known along with the total S + P time in ms derived from Hz, the total “pause” time in ms can be derived using the following general relationship: P = [1000 ms – (Hz × SL)]/Hz. It has also been proposed, that the language of neu- rons can be written in any of a number of fre- quency-encoded formats including Hz, S/P and musical notations and can be translated into any of the oral, writ- ten or symbolic human languages as well [1]. Impor- tantly, using artificial electronically generated frequen- cies that mimic the frequencies of recorded natural neu- ronal words, it has been demonstrated that it is possible not only to record these neuronal words, but also to communicate directly with the central nervous system (CNS) of rats. Where this has been done, the manufac- tured words have been shown to elicit the same behav- ioral responses in rats that would have been generated by exposure to a specific environmental stimulus [9]. 2.5. The Dictionary of Neuronal Words and their Representational Nature The dictionary of neuronal S/P words in an ms time- frame is relatively short, being limited at its upper level by the absolute and relative neuronal refractory periods and at its lower level by physiological requirements such as maintenance of the human heart rate at 68 beats/min (1.13 Hz). With the average spike including an absolute refractory period of 1 ms duration followed by a relative refractory period of about 2 ms, the highest possible frequency would be S1P2 or 333 Hz. If the system were driven by a strong enough input eliminating the relative refractory period altogether, the highest possible fre- quency might be S1P0 or 1,000 Hz. Since the brain’s primary form of communication, both internally and with the outside world, is in the form of these electrophysiological messages, it follows that neuronal words must also be highly representational in nature. For example, audible sound in many animals may range up to 20,000 Hz and visible light is in the ![]() M. H. Baslow / Natural Science 2 (2010) 205-211 Copyright © 2010 SciRes. OPEN ACCESS 209 Figure 3. A “dark room” paradigm of brain function. Table 1. List of several neuronal S/P words and their meanings. Organism Sensor Word Meaning Reference Blowfly sensillum salt S 1P499 NaCl 0.10 M [8] S 1P45 0.20 S 1P27 0.25 S 1P18 0.50 S 1P12 1.00 S 1P9 2.00 S 1P7 3.00 Ground beetle Sensillum salt S 1P1000 NaCl 0.001 M [11] S 1P71 0.01 S 1P29 0.10 S 1P23 1.00 Hamster taste cells acid S 1P286 pH 2.5 [12] S 1P312 3.0 S 1P1999 4.3 S 1P4000 5.0 Cat brain hypothalamus glucose glucosensing steady-state S 1P10000 normal Glc level [13] Glc i.v. 30 min S 1P2000 elevated Glc level Rat taste cells quinine S 1P21 quinine 0.01 mM [9] Rat brain hippocampal sound S1P499 frequency 2 kHz [10] neuron S 1P142 10 kHz Guinea pig brain GABAergic H 2O2 S 1P53 H 2O2 0.0 mM [14] neurons S 1P40 1.5 range of 1014 Hz. For the brain to comprehend its exter- nal environment, these frequencies must first be con- verted into representations of those wavelengths at less than 1000 Hz, with the same meanings as the original signals, which can then be transmitted by neurons within the CNS network. These representations can also be “memorized” in the form of structural and biochemical changes in the dendrite-synapse-dendrite (DSD) fields ![]() M. H. Baslow / Natural Science 2 (2010) 205-211 Copyright © 2010 SciRes. OPEN ACCESS 210 between neurons, and later recalled to “imagine” the nature of the original wavelengths even without external input. For example, one can imagine “in the minds eye” the color “red” with the eyes closed, and with eyes open can also compare a newly observed representation of red with that which was previously seen and stored in mem- ory. This phenomenon is illustrated in Figure 3 where a specific sound tone of 2 kHz impinging on the ear is converted into a representational neuronal word at 2 Hz for CNS network processing. In this illustration, the translation by a sense organ of the specific frequency-encoded environmental informa- tion for the approximate musical tone B6 (1975.53 Hz) is illustrated. The sound sense organ first converts the tone into a brain frequency-encoded S/P word representation for B6 at 2 Hz (S1P499) that is then compared within the CNS network to auditory area DSD memory constructs. During this comparison related historical documents in other brain areas may also be probed for relevant infor- mation. Upon an executive command, appropriate mus- cles can also be activated to reproduce the 1975.53 Hz frequency, exporting it to another organism and also sending it back to the sense organ where it can be com- pared to the original tone. Importantly, the S/P word for the tone B6 or any other musical tone can also be synthe- sized de novo by the brain from memory engrams with- out external input and can be “heard” within the brain as recalled sounds or melodies. All of these functions occur in a ms/sub-ms timeframe and apply to any other sensed parameter, whether derived internally or external to the brain. The specific auditory data presented in Figure 3 is adapted from rat experiments [10]. 2.6. Examples of Neuronal Words and their Meanings In Table 1 descriptions of some S/P words and their meanings are presented. In each of these cases, the S/P words have been derived from frequency data by using an average SL including an absolute refractory period of 1.0 ms, and rounded to the nearest integer. However, it is also apparent that neurons can operate in a sub-millisecond timeframe [10], which is in keeping with the microsecond timeframe dictated by physiological demands and com- munication networking requirements of the brain. 3. CONCLUSIONS In this paper it is proposed that neurons possess natural language in the form of specific neuronal words, phrases and sentences, and evidence is provided that when spe- cific neuronal words are known, it is possible to mimic them and generate electronic words to communicate intelligently with the CNS. While most investigative recordings of neuronal activity are in the form of Hz, the differences between Hz and word formats have been described, and a case has been made that the word for- mat is the only format that can be physiologically asso- ciated with the release of specific quanta of neurotrans- mitters at synapses and is therefore more representative of the potential richness of information that can be transmitted by neurons. In addition, based on physio- logical limitations associated with the bioenergetic na- ture of neuronal AP’s, it has been shown that much of the information about the external environment that is transmitted to the brain must first be reduced to a fre- quency-encoded representation of that information that can be communicated at < 1000 Hz. These representa- tions can be acted upon immediately, memorized when appropriate, and the memorized information recalled as needed in the form of such representations within the brain. Of note, in humans and other animals these inter- nal representations can also be converted back into their original electromagnetic spectrum frequencies by exter- nally re-creating the original environmental source such as by reproducing a particular memorized sound fre- quency. 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